The Duke Comprehensive Cancer Center was founded as a matrix center within the Duke University School of Medicine in 1972 and the Duke Cancer Institute (DCI) was created as a new administrative entity within Duke Medicine in October, 2010, with authority and responsibility for all cancer-related activities at Duke University and in the Duke University Health System. The DCI was started with significant investments from Duke Medicine, including a new $243M clinical care outpatient facility, over $60 million of new funds available to support new initiatives, a formula for ongoing investment by the Duke Health System to support ongoing and new DCI initiatives, and additional laboratory and office-based research space. These new commitments were in addition to the clinical space and administrative and Shared Resource lab space already under DCI control and the many laboratories in the Duke School of Medicine and University housing DCI members. The first DCI Executive Director, Michael Kastan, M.D., Ph.D., was hired in August, 2011, followed by major changes in administrative infrastructure, leadership positions and roles, and Cancer Center committees. CCSG Programs and Shared Resources were re-organized, investments were made in high-priority areas, and mechanisms established to more effectively facilitate communication and collaborations among DCI faculty. The DCI, which currently consists of 354 members from 25 departments within 5 schools at Duke University (Medicine, Nursing, Arts and Sciences, Engineering, and Business), promotes collaborations between faculty and staff involved in cancer care, research, and education within both Duke University and the Duke University Health System. It is organized as 9 multi-disciplinary research programs (2 basic discovery, 1 population science, and 6 translational) whose work is supported by 13 Shared Resources (8 lab-based and 5 supporting translational/ clinical/ population research activities). On average, approximately 6000 new cancer patients are seen each year at Duke University Hospital (DUH); during the previous 5 calendar years, an average of approximately 1900 patients per year were enrolled on therapeutic clinical trials at DUH and partner sites, the vast majority of which were at DUH. Almost two-thirds of the DCI therapeutic clinical trials represent early phase research (pilot, phase I, phase II). DCI members are supported by over $242M of external cancer- related grant support, $160M of which is peer-reviewed. DCI grant support includes 51 multi-investigator projects and 91 training and fellowship awards. DCI members published over 8000 papers in peer-reviewed journals during the past funding period, ~39% of which represent collaborative efforts between DCI investigators (12% intra-program, 21% inter-program, and 6% both). The DCI will continue to utilize effective oversight and strategic planning to integrate all cancer-related activities in it purview, from basic research to translational studies to clinical and population investigation to patient care to community outreach to regional/national strategies to global cancer.